雌激素受体α36影响他莫昔芬治疗乳腺癌的分子机制研究进展_West China Medical Journal

Authors：

 张又 , 华慧 , 李楠静 ,  罗婷

四川大学华西医院分子医学研究中心（成都 610041）;

Corresponding author：

罗婷, Email: tina621@163.com

Keywords：

雌激素受体α36; 乳腺癌; 他莫昔芬; 内分泌治疗; 耐药

DOI：

10.7507/1002-0179.201600266

Video：

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Abstract Full text Figures/Tables Video References Cited by

雌激素受体α（ERα）36 是相对分子质量为36×10³ 的ERα 的一种亚型。它缺失转录活性区1（AF-1）和转录活性区2（AF-2），在生物学功能上与ERα66 有很大不同。ERα36 主要位于细胞膜和细胞质中，主要参与膜介导的非基因组信号通路。它能抑制ERα66 介导的传统基因组信号通路，引起不同蛋白的层级磷酸化反应，增加乳腺癌和子宫内膜癌细胞及其干细胞的耐药性、迁移能力和浸润能力。研究显示ERα36 与乳腺癌采用他莫昔芬治疗耐药有密切关系。对ERα36 的深入研究有助于深化乳腺癌发生发展的理论知识，为内分泌治疗药物选择提供可能的理论依据。

Citation： 张又, 华慧, 李楠静, 罗婷. 雌激素受体α36影响他莫昔芬治疗乳腺癌的分子机制研究进展. West China Medical Journal, 2016, 31(5): 986-990. doi: 10.7507/1002-0179.201600266 Copy

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32.	Yin L, Zhang XT, Bian XW, et al. Disruption of the ER-a36-EGFR/ HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells[J]. PLoS One, 2014, 9(9): e107369.

1. Cheung KL. Endocrine therapy for breast cancer: an overview[J]. Breast, 2007, 16(4): 327-343.
2. Lim E, Metzger-Filho O, Winer EP. The natural history of hormone receptor-positive breast cancer[J]. Oncology (Williston Park), 2012, 26(8): 688-694, 696.
3. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials[J]. Lancet,2005, 365(9472): 1687-1717.
4. Goldhirsch A, Colleoni RD, Gelber M. Endocrine therapy of breast cancer[J]. Oncol, 2002, 13(4): 61–68.
5. Jordan VC. Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer[J]. Endocr Relat Cancer, 2014, 21(3): R235-R246.
6. García-Becerra R, Santos N, Díaz L, et al. Mechanisms of resistance to endocrine therapy in breast cancer: focus on signaling pathways, miRNAs andgenetically based resistance[J]. Int J Mol Sci, 2012, 14(1): 108-145.
7. Cheng SB, Quinn JA, Graeber CT, et al. Down-modulation of the G-protein-coupled estrogen receptor, GPER, from the cell surface occurs via a trans-Golgi-proteasome pathway[J]. J Biol Chem, 2011, 286(25): 22441-22455.
8. Nass N, Kalinski T. Tamoxifen resistance: from cell culture experiments towards novel biomarkers[J]. Pathol Res Pract, 2015, 211(3): 189-197.
9. Li L, Haynes MP, Bender JR. Plasma membrane localization and function of the estrogen receptor alpha variant (ER46) in human endothelial cells[J]. Proc Natl Acad Sci USA, 2003, 100(8): 4807-4812.
10. Wang Z, Zhang X, Shen P, et al. Identifcation, cloning, and expression of human estrogen receptor-alpha36, a novel variant of human estrogen receptor-alpha66[J]. Biochem Biophys Res Commun, 2005, 336(4): 1023-1027.
11. Hirata S, Shoda T, Kato J, et al. Isoform/variant mRNAs for sex steroid hormone receptors in humans[J]. Trends Endocrinol Metab, 2003, 14(3): 124-129.
12. Deng H, Huang X, Fan J, et al. A variant of estrogen receptoralpha, ER-alpha36 is expressed in human gastric cancer and is highlycorrelated with lymph node metastasis[J]. Oncol Rep, 2010, 24(1): 171-176.
13. Greene GL, Gilna P, Waterfeld M, et al. Sequence and expression of human estrogen receptor complementary DNA[J]. Science, 1986, 231(4742): 1150-1154.
14. Kong EH, Pike AC, Hubbard RE. Structure and mechanism of the oestrogen receptor[J]. Biochem Soc Trans, 2003, 31(1): 56-59.
15. Rao J, Jiang X, Wang Y, et al. Advances in the understanding of the structure and function of ER-α36, a novel variant of human estrogen receptor-alpha[J]. J Steroid Biochem Mol Biol, 2011, 127(3-5): 231-237.
16. Wang Z, Zhang X, Shen P, et al. A variant of estrogen receptor- alpha, hER-alpha36: transduction of estrogen- and antiestrogendependentmembrane- initiated mitogenic signaling[J]. Proc Natl Acad Sci USA, 2006, 103(24): 9063-9068.
17. Ma d a i o R A , S p a l l e t t a G , C r a v e l l o L , e t a l . Overcoming endocrine resistance in metastatic breast cancer: Current evidence and future directions[J]. World J Clin Oncol, 2014, 5(5): 990-1001.
18. Zhang X, Wang ZY. Estrogen receptor-α variant, ER-α36, is involved in tamoxifen resistance and estrogen hypersensitivity[J]. Endocrinology, 2013, 154(6): 1990-1998.
19. Vranic S, Gatalica Z, Deng H, et al. ER-α36, a novel isoform of ER- α66, is commonly over-expressed in apocrine and adenoid cystic carcinomas of the breast[J]. J Clin Pathol, 2011, 64(1): 54-57.
20. Lin SL, Yan LY, Zhang XT, et al. ER-alpha36, a variant of ERalpha, promotes tamoxifen agonist action in endometrial cancer cells via theMAPK/ERK and PI3K/Akt pathways[J]. PLoS One, 2010, 5(2): e9013.
21. Zhang X, Ding L, Kang L, e t a l . E s t r o g e n receptoralpha 36 mediates mitogenic antiestrogen signaling in ERnegative breast cancer cells[J]. PLoS One, 2012, 7(1): e30174.
22. Wang X, Hills LB, Huang YH. Lipid and protein co-regulation of PI3K effectors Akt and Itk in lymphocytes[J]. Front Immunol, 2015(6): 117.
23. Xia B, Tian C, Guo S, et al. c-Myc plays part in drug resistance mediated by bone marrow stromal cells in acute myeloid leukemia[J]. Leuk Res, 2015, 39(1): 92-99.
24. Lee LM, Cao J, Deng H, et al. ER-alpha36, a novel variant of ERalpha, is expressed in ER-positive and -negative human breast carcinomas[J]. Anticancer Res, 2008, 28(1B): 479-483.
25. Zhang XT, Kang LG, Ding L, et al. A positive feedback loop of ER-α3 6 /EGFR promot e s ma l i gnant g rowth of ERnegative breast cancer cells[J]. Oncogene, 2011, 30(7): 770-780.
26. Tu BB, Lin SL, Yan LY, et al. ER-α36, a novel variant of estrogen receptor α, is involved in EGFR-related carcino-genesis in endometrial cancer[J]. Am J Obstet Gynecol, 2011, 205(3): e1-e6.
27. Chung YL, Sheu ML, Yang SC, et al. Resistance to tamoxifen induced apoptosis is associated with direct interaction between Her2/neu andcell membrane estrogen receptor in breast cancer[J]. Cancer, 2002, 97(3): 306-312.
28. Shou J, Massarweh S, Osborne CK, et al. Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/ HER2-positive breast cancer[J]. J Natl Cancer Inst, 2004, 96(12): 926-935.
29. Kang L, Guo Y, Zhang X, et al. A positive cross-regulation of HER2 and ER-α36 controls ALDH1 positive breast cancer cells[J]. J Steroid Biochem Mol Biol, 2011, 127(3/4/5): 262-268.
30. Li G, Zhang J, Jin K, et al. Estrogen receptor-alpha 36 is involved in development of acquired tamoxifen resistance via regulating the growth status Switch in breast cancer cells[J]. Mol Oncol, 2013, 7(3): 611-624.
31. Deng H, Yin L, Zhang XT, et al. ER-α variant ER-α36 mediates antiestrogen resistance in ER-positive breast cancer stem/ progenitor cells[J]. J Steroid Biochem Mol Biol, 2014, 144(B): 417-426.
32. Yin L, Zhang XT, Bian XW, et al. Disruption of the ER-a36-EGFR/ HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells[J]. PLoS One, 2014, 9(9): e107369.

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West China Medical Journal

雌激素受体α36影响他莫昔芬治疗乳腺癌的分子机制研究进展

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